| Autor: |
Flower, Michael, Lomeilkaite, Vilila, Ciosi, Marc, Cumming, Sarah, Morales, Fernando, Lo, Kitty, Hensman Moss, Davina, Jones, Lesley, Holmans, Peter, Monckton, Darren G., Tabrizi, Sarah J., Kraus, Peter, Hoffman, Rainer, Tobin, Alan, Borowsky, Beth, Keenan, S., Whitlock, Kathryn B., Queller, Sarah, Campbell, Colin, Wang, Chiachi, Langbehn, Doug, Axelson, Eric, Johnson, Hans, Acharya, Tanka, Cash, Dave M., Frost, Chris, Jones, Rebecca, Jurgens, Caroline, ‘t Hart, Ellen P., van der Grond, Jeroen, Witjes- Ane, Marie-Noelle N., Roos, Raymund A. C., Dumas, Eve M., van den Bogaard, Simon J. A., Stopford, Cheryl, Craufurd, David, Callaghan, Jenny, Arran, Natalie, Rosas, Diana D., Lee, S., Monaco, W., O’Regan, Alison, Milchman, Cassie, Frajman, E., Labuschagne, Izelle, Stout, Julie, Campbell, Melissa, Andrews, Sophie C., Bechtel, Natalie, Reilmann, Ralf, Bohlen, Stefan, Kennard, Chris, Berna, Claire, Hicks, Stephen, Durr, Alexandra, Pourchot, C., Bardinet, Eric, Nigaud, Kevin, Valabre`gue, Romain, Lehericy, Stephane, Marelli, Cecilia, Jauffret, Celine, Justo, Damian, Leavitt, Blair, Decolongon, Joji, Sturrock, Aaron, Coleman, Alison, Dar Santos, Rachelle, Patel, A., Gibbard, Claire, Whitehead, Daisy, Wild, Ed, Owen, Gail, Crawford, Helen, Malone, Ian, Lahiri, Nayana, Fox, Nick C., Hobbs, Nicola Z., Scahill, Rachael I., Ordidge, Roger, Pepple, Tracey, Read, Joy, Say, Miranda J., Landwehrmeyer, Bernhard, Daidj, Ferroudja, Bassez, Guillaume, Lignier, Baptiste, Couppey, Florence, Delmas, Stéphanie, Deux, Jean-François, Hankiewicz, Karolina, Dogan, Celine, Minier, Lisa, Chevalier, Pascale, Hamadouche, Amira, Catt, Michael, van Hees, Vincent, Catt, Sharon, Schwalber, Ameli, Dittrich, Juliane, Kierkegaard, Marie, Wenninger, Stephan, Schoser, Benedikt, Schüller, Angela, Stahl, Kristina, Künzel, Heike, Wolff, Martin, Jellinek, Anna, Moreno, Cecilia Jimenez, Gorman, Grainne, Lochmüller, Hanns, Trenell, Michael, van Laar, Sandra, Wood, Libby, Cassidy, Sophie, Newman, Jane, Charman, Sarah, Steffaneti, Renae, Taylor, Louise, Brownrigg, Allan, Day, Sharon, Atalaia, Antonio, Raaphorst, Joost, Okkersen, Kees, Engelen, Baziel van, Nikolaus, Stephanie, Cornelissen, Yvonne, van Nimwegen, Marlies, Maas, Daphne, Klerks, Ellen, Bouman, Sacha, Knoop, Hans, Heskamp, Linda, Heerschap, Arend, Rahmadi, Ridho, Groot, Perry, Heskes, Tom, Kapusta, Katarzyna, Glennon, Jeffrey, Abghari, Shaghayegh, Aschrafi, Armaz, Poelmans, Geert, Treweek, Shaun, Hogarth, Fiona, Littleford, Roberta, Donnan, Peter, Hapca, Adrian, Hannah, Michael, McKenzie, Emma, Rauchhaus, Petra, Cumming, Sarah A., Adam, Berit, Faber, Catharina, Merkies, Ingemar, TRACK-HD Investigators, OPTIMISTIC Consortium |
| Přispěvatelé: |
Neurology, ANS - Neurodegeneration, APH - Mental Health, Medical Psychology |
| Rok vydání: |
2019 |
| Předmět: |
|
| Zdroj: |
Brain, vol. 142(7), 1876-1886
Kérwá
Universidad de Costa Rica
instacron:UCR
Brain, 142(7), 1876-1886. Oxford University Press
Brain |
| ISSN: |
1460-2156
0006-8950 |
| DOI: |
10.1093/brain/awz115 |
| Popis: |
A genome-wide association study recently identified an MSH3/DHFR locus associated with Huntington’s disease progression. Flower, Lomeikaite et al. identify tandem repeat variants at this locus, and show that a three-repeat allele is associated with reduced somatic expansion, delayed onset and slower progression in Huntington’s disease and myotonic dystrophy type 1.
The mismatch repair gene MSH3 has been implicated as a genetic modifier of the CAG·CTG repeat expansion disorders Huntington’s disease and myotonic dystrophy type 1. A recent Huntington’s disease genome-wide association study found rs557874766, an imputed single nucleotide polymorphism located within a polymorphic 9 bp tandem repeat in MSH3/DHFR, as the variant most significantly associated with progression in Huntington’s disease. Using Illumina sequencing in Huntington’s disease and myotonic dystrophy type 1 subjects, we show that rs557874766 is an alignment artefact, the minor allele for which corresponds to a three-repeat allele in MSH3 exon 1 that is associated with a reduced rate of somatic CAG·CTG expansion (P = 0.004) and delayed disease onset (P = 0.003) in both Huntington’s disease and myotonic dystrophy type 1, and slower progression (P = 3.86 × 10−7) in Huntington’s disease. RNA-Seq of whole blood in the Huntington’s disease subjects found that repeat variants are associated with MSH3 and DHFR expression. A transcriptome-wide association study in the Huntington’s disease cohort found increased MSH3 and DHFR expression are associated with disease progression. These results suggest that variation in the MSH3 exon 1 repeat region influences somatic expansion and disease phenotype in Huntington’s disease and myotonic dystrophy type 1, and suggests a common DNA repair mechanism operates in both repeat expansion diseases. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
